title: Genotype phenotype correlations of cardiac beta-myosin heavy chain mutations in Indian patients with hypertrophic and dilated cardiomyopathy.
abstract: The aim of the current study was to determine the frequency of mutations in the beta-myosin heavy chain gene (MYH7) in a cohort of hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) and their families, and to investigate correlations between genotype and phenotype. About 130 consecutive patients diagnosed with HCM or DCM (69 with HCM and 61 with DCM) attending the cardiology clinic of Post Graduate Institute of Medical Education and Research were screened for mutations in the MYH7 gene. The control group for genetic studies consisted of 100 healthy subjects. We report 14 mutations in 6 probands (5 probands in HCM and 1 proband in DCM) and their family members. Out of these 6 mutations, 3 are new and are being reported for the first time. One known mutation (p.Gly716Arg) was found to be "de novo" which resulted in severe asymmetric septal hypertrophy (31 mm) and resulted in the sudden cardiac death (SCD) of the proband at the age of 21 years. Further, a DCM causing novel mutation p.Gly377Ser was identified which resulted in the milder phenotype. The present study shows that there is genetic and phenotypic heterogeneity of cardiomyopathies in Indian population. Further, the location and type of mutation in a given sarcomeric gene determines the severity and phenotypic plasticity in cardiomyopathies.
authors.affiliation: Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Taranjit Singh
authors.initials: TS
authors.lastname: Rai
authors.forename: Shamim
authors.initials: S
authors.lastname: Ahmad
authors.forename: Ajay
authors.initials: A
authors.lastname: Bahl
authors.forename: Monica
authors.initials: M
authors.lastname: Ahuja
authors.forename: Tarunveer Singh
authors.initials: TS
authors.lastname: Ahluwalia
authors.forename: Balvinder
authors.initials: B
authors.lastname: Singh
authors.forename: K K
authors.initials: KK
authors.lastname: Talwar
authors.forename: Madhu
authors.initials: M
authors.lastname: Khullar
mesh_terms: D000328:Adult; D024722:Cardiac Myosins / Q000235:genetics / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004252:DNA Mutational Analysis; D004452:Echocardiography; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D010375:Pedigree; D010641:Phenotype; D024723:Ventricular Myosins / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: C501641:MYH7 protein, human; D024722:Cardiac Myosins; D024723:Ventricular Myosins; D018995:Myosin Heavy Chains